TM-13 * DIMINISHED PROGRESSION OF GLIOBLASTOMA WITH A SUPPLEMENTED HIGH-FAT LOW-CARBOHYDRATE DIET

Abstract

Glioblastoma [GB] is the deadliest and most malignant type of brain tumor, with a median survival less than 12 months. Research into tumor metabolism and the Warburg Effect have shed new light on an idea that puts energy disparities at the forefront for new and innovative treatment options for patients. Tumor cells have an established dependence on glucose that plays a significant role in growth and survival. The human body retains secondary energy sources that can be utilized in times of starvation and glucose deprivation. By exchanging ketones (β-hydroxybutyrate) for glucose as the primary energy source in the body we can slow the progression of glioblastoma's. Conventional methods for entering ketosis, such as the ketogenic diet (KD), have been tested clinically with variable success due to high rates of side effects and low diet palatability, reducing compliance. Therefore, we have created a supplemented high-fat low-carbohydrate (sHFLC) Diet [10%C;60%F(30%MCT);30%P] that induces the two key physiological features of the KD but is more nutritionally sound and palatable. Dietary effectiveness was tested in vitro using patient derived GB neurosphere cell lines and in vivo using NOD/SCID xenografts. In culture, individually reducing glucose and increasing ketones resulted in a significant reduction in tumor cell viability that was enhanced by the combination of low glucose and elevated ketones. In vivo we demonstrate that animals fed the sHFLC exhibited a significant decline in circulating glucose (96.01mg/dL ±14.25 vs 165.1mg/dL ±20.87, p < .0001) and elevation in circulating ketones (1.798mmol ±1.121 vs .400mmol ±.115, p < .0001), slowed tumor progression (390.18mm3 ±133 vs 1020.69mm3 ±368.9, p < .0001; at 28 days post-implant) and increased survival (46.5 ±13.16 days vs 34.5 ±4.2 days, p < .0001) compared to normal fed controls. Additionally the sHFLC better maintained animal body weight as well as overall appearance when compared to the KD (28.78g ±1.812 vs 24.45g ±5.999, p < .001).